10 research outputs found
Recommended from our members
Molecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic Fibrosis.
To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs
Creating a 3D microbial and chemical snapshot of a human habitat
Kapono CA, Morton JT, Bouslimani A, et al. Creating a 3D microbial and chemical snapshot of a human habitat. Scientific Reports. 2018;8(1): 3669
Shared Bioinformatics Databases within the Unipro UGENE Platform
Unipro UGENE is an open-source bioinformatics toolkit that integrates popular tools along with original instruments for molecular biologists within a unified user interface. Nowadays, most bioinformatics desktop applications, including UGENE, make use of a local data model while processing different types of data. Such an approach causes an inconvenience for scientists working cooperatively and relying on the same data. This refers to the need of making multiple copies of certain files for every workplace and maintaining synchronization between them in case of modifications. Therefore, we focused on delivering a collaborative work into the UGENE user experience. Currently, several UGENE installations can be connected to a designated shared database and users can interact with it simultaneously. Such databases can be created by UGENE users and be used at their discretion. Objects of each data type, supported by UGENE such as sequences, annotations, multiple alignments, etc., can now be easily imported from or exported to a remote storage. One of the main advantages of this system, compared to existing ones, is the almost simultaneous access of client applications to shared data regardless of their volume. Moreover, the system is capable of storing millions of objects. The storage itself is a regular database server so even an inexpert user is able to deploy it. Thus, UGENE may provide access to shared data for users located, for example, in the same laboratory or institution. UGENE is available at: http://ugene.net/download.html
Coupling Targeted and Untargeted Mass Spectrometry for Metabolome-Microbiome-Wide Association Studies of Human Fecal Samples
Increasing appreciation
of the gut microbiome’s role in
health motivates understanding the molecular composition of human
feces. To analyze such complex samples, we developed a platform coupling
targeted and untargeted metabolomics. The approach is facilitated
through split flow from one UPLC, joint timing triggered by contact
closure relays, and a script to retrieve the data. It is designed
to detect specific metabolites of interest with high sensitivity,
allows for correction of targeted information, enables better quantitation
thus providing an advanced analytical tool for exploratory studies.
Procrustes analysis revealed that untargeted approach provides a better
correlation to microbiome data, associating specific metabolites with
microbes that produce or process them. With the subset of over one
hundred human fecal samples from the American Gut project, the implementation
of the described coupled workflow revealed that targeted analysis
using combination of single transition per compound with retention
time misidentifies 30% of the targeted data and could lead to incorrect
interpretations. At the same time, the targeted analysis extends detection
limits and dynamic range, depending on the compounds, by orders of
magnitude. A software application has been developed as a part of
the workflow to allows for quantitative assessments based on calibration
curves. Using this approach, we detect expected microbially modified
molecules such as secondary bile acids and unexpected microbial molecules
including <i>Pseudomonas</i>-associated quinolones and rhamnolipids
in feces, setting the stage for metabolome-microbiome-wide association
studies (MMWAS)
Recommended from our members
Three-Dimensional Microbiome and Metabolome Cartography of a Diseased Human Lung.
Our understanding of the spatial variation in the chemical and microbial makeup of an entire human organ remains limited, in part due to the size and heterogeneity of human organs and the complexity of the associated metabolome and microbiome. To address this challenge, we developed a workflow to enable the cartography of metabolomic and microbiome data onto a three-dimensional (3D) organ reconstruction built off radiological images. This enabled the direct visualization of the microbial and chemical makeup of a human lung from a cystic fibrosis patient. We detected host-derived molecules, microbial metabolites, medications, and region-specific metabolism of medications and placed it in the context of microbial distributions in the lung. Our tool further created browsable maps of a 3D microbiome/metabolome reconstruction map on a radiological image of a human lung and forms an interactive resource for the scientific community
Feature-based molecular networking in the GNPS analysis environment
Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry
Recommended from our members
Feature-based molecular networking in the GNPS analysis environment.
Molecular networking has become a key method to visualize and annotate the chemical space in non-targeted mass spectrometry data. We present feature-based molecular networking (FBMN) as an analysis method in the Global Natural Products Social Molecular Networking (GNPS) infrastructure that builds on chromatographic feature detection and alignment tools. FBMN enables quantitative analysis and resolution of isomers, including from ion mobility spectrometry